Maintenance of oxygen delivery sufficient to meet myocardial metabolic demands is of critical importance for normal cardiac pump function. Knowledge of the physiologic mechanisms which regulate myocardial blood flow and oxygen extraction during various hemodynamic and metabolic stresses is essential for developing and evaluating therapeutic interventions for situations in which oxygen supply and demand are not precisely matched (e.g. ischemic heart disease). The overall objective of this study is to assess the relative importance of metabolic and myogenic factors in the local regulation of coronary blood flow. Specific aims are (1) to determine the effects of altering the balance between myocardial oxygen supply and demand on the degree of coronary vasoregulation following: (a) changes in perfusion pressure (autoregulation), (b) temporary coronary artery occlusion (reactive hyperemia), (c) decreases in arterial oxygen content (hypoxic vasodilation), and (d) increases in metabolic activity (metabolic hyperemia); (2) to characterize the dynamics of flow regulation and oxygen extraction during myocardial reactive hyperemia with restricted and unrestricted arterial inflow; (3) to determine the influence of metabolic state on reactive hyperemia during the preocclusion, occlusion and postocclusion periods; and (4) to assess the role of a myogenic mechanism in the maintenance of basal coronary vascular tone and in modulating changes in coronary vascular resistance during autoregulation and reactive hyperemia. These studies will be performed largely in closed chest anesthetized dogs. Coronary blood flow, perfusion pressure, and myocardial oxygen extraction and uptake will be continuously monitored. Myocardial oxygen supply will be altered by changing coronary arterial oxygen content and by using intracoronary vasoactive drugs to change baseline flow. Myocardial oxygen demands will be altered by changing heart rate, ventricular afterload, or contractility. The role of a myogenic mechanism will be evaluated by determining the effects of coronary venous hypertension on baseline coronary vascular resistance and blood flow regulation. These studies will provide important information concerning the basic vasoregulatory mechanisms for maintaining adequate myocardial oxygenation under a variety of conditions.